Obesity and type 2 diabetes (T2D) are growing public health concerns. Although diet is a well-known factor in the development of these conditions, public health efforts in dietary behavior modification have met with limited success. Bitter, sweet and salty taste preferences are important determinants of dietary intake. Taste may also serve functions that may directly impact metabolic health. Specific taste preferences might therefore impact risk of obesity and T2D, but human evidence supporting this notion is limited. Inter-individual variability in taste- preferences is rarely considered in population studies. Knowledge of the genetic determinants of this variation can be especially useful in furthering our understanding of taste biology and to elucidate the role that preferences for bitter, sweet, or salty foods may have in metabolic disease development. Such knowledge can also be used in designing more effective interventions for the prevention and treatment of these conditions. Previous studies aimed to identify taste genetic loci have taken a biology-to-behavior approach to gene discovery. A powerful, agnostic approach is now possible with advancements in the genetic field and the availability of large sample sizes. Taste preferences, however, are not commonly measured in large population-based studies; thus limiting both traditional and genetic epidemiological studies of these traits. The first goal of this proposal is to develop taste preference scores that can be derived from existing food preference or consumption data. Our second goal is to identify genetic loci associated with human taste preferences and then to apply this molecular knowledge to deciphering the role taste preferences play in obesity and T2D development. We will use taste preference scores constructed from food consumption data and existing genome-wide scans available from population-based cohorts: the Nurses' Health Study, Health Professionals Follow-up Study and the Women's Genome Health Study. We will replicate the most promising loci in the CHARGE consortium and then examine their impact on obesity and T2D risk using available results from GIANT and DIAGRAM; large consortia committed to the genetic study of anthropometry and T2D, respectively. By combining advanced genetic knowledge and technology, sophisticated statistical tools, a well-defined trait and a sufficiently sized sample, our research will provide novel insight into factors governing human taste preferences and the impact they have on obesity and T2D development. The proposed research plan aligns with Priorities I and III of NIDCD's Smell and Taste program: we seek to understand 'normal' variation in taste preference and how this variation impacts metabolic disease at a population level. Moreover, results of this study will foster new lines of investigatin for reducing risk of diet-related conditions and for developing novel behavioral and pharmacological avenues of treatment and prevention and thus indirectly addresses the program's fourth priority area.